Skip to main content Accessibility help
×
Hostname: page-component-857557d7f7-9f75d Total loading time: 0 Render date: 2025-11-30T20:46:22.931Z Has data issue: false hasContentIssue false

Chapter 3 - Neurorestoration – A New Synthesis: Repair, Replace, and Optimize

from Section II - Ideas and Concepts in Modern Neurosurgical Innovation

Published online by Cambridge University Press:  aN Invalid Date NaN

Benjamin Hartley
Affiliation:
Weill Cornell Medical Center
Philip E. Stieg
Affiliation:
Weill Cornell Medical College
Rohan Ramakrishna
Affiliation:
Weill Cornell Medical College
Michael L. J. Apuzzo
Affiliation:
Adjunct of Yale Medical School and Weill Cornell Medical College
Get access

Summary

Functional restoration of the human nervous system remains the “Holy Grail” for the clinical neurosciences. Traditional teachings suggested that the central nervous system, comprised of the brain and spinal cord, was incapable of regeneration or repair, especially in adults. Thus, the entire focus of the clinical neurosciences was aimed at preserving function, with restoration being impractical if not impossible. However, in the past decades, multifaceted proofs of concept in humans are providing convincing evidence that through rapid developments in neuroscience, neural engineering, and functional neuroimaging, neurorestoration will soon be practical even in adults. Here, the authors describe a practical working definition of “neurorestoration” as interwoven concepts of regenerative medicine (repair), neuroprosthetics (replace), and neuromodulation-enhanced learning (optimize). A comprehensive review of the topics covered is certainly well beyond the scope of this discussion.

Information

Type
Chapter
Information
Neurosurgery
Beyond the Cutting Edge
, pp. 28 - 42
Publisher: Cambridge University Press
Print publication year: 2025

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Thompson, L., Fetal transplants show promise. Science 257, 868, 870 (1992).10.1126/science.1502548CrossRefGoogle ScholarPubMed
Institute of Medicine (US) Conference Committee on Fetal Research and Applications, Fetal Research and Applications: A Conference Summary (National Academies Press (US), Washington (DC), 1994; http://www.ncbi.nlm.nih.gov/books/NBK232011/).Google Scholar
Liu, C. Y., Apuzzo, M. L. J., Tirrell, D. A., Engineering of the extracellular matrix: working toward neural stem cell programming and neurorestoration – concept and progress report. Neurosurgery 52, 1154 (2003).Google ScholarPubMed
The Nobel Prize in Physiology or Medicine 2012, The Nobel Prize. https://www.nobelprize.org/prizes/medicine/2012/press-release/.Google Scholar
Wadman, M., Stem cells ready for prime time. Nature 457, 516 (2009).10.1038/457516aCrossRefGoogle ScholarPubMed
McKenna, S. L., Ehsanian, R., Liu, C. Y., Steinberg, G. K., Jones, L., Lebkowski, J. S., Wirth, E., Fessler, R. G., Ten-year safety of pluripotent stem cell transplantation in acute thoracic spinal cord injury. J Neurosurg Spine 37, 321–30 (2022).10.3171/2021.12.SPINE21622CrossRefGoogle ScholarPubMed
Fessler, R. G., Liu, C. Y., McKenna, S., Fessler, R. D., Lebkowski, J. S., Priest, C. A., Wirth, E. D., Safety of direct injection of oligodendrocyte progenitor cells into the spinal cord of uninjured Göttingen minipigs. J Neurosurg Spine 35, 389–97 (2021).10.3171/2020.12.SPINE201853CrossRefGoogle ScholarPubMed
Fessler, R. G., Ehsanian, R., Liu, C. Y., Steinberg, G. K., Jones, L., Lebkowski, J. S., Wirth, E. D., McKenna, S. L., A phase 1/2a dose-escalation study of oligodendrocyte progenitor cells in individuals with subacute cervical spinal cord injury. J Neurosurg Spine 37, 812–20 (2022).10.3171/2022.5.SPINE22167CrossRefGoogle ScholarPubMed
Bourzac, K., Neuroscience: new nerves for old. Nature 540, S52–4 (2016).10.1038/540S52aCrossRefGoogle ScholarPubMed
Regalado, A., After 25 years of hype, embryonic stem cells are still waiting for their moment, MIT Technology Review (2023). https://www.technologyreview.com/2023/08/09/1077580/embryonic-stem-cells-25-years-treatments/.Google Scholar
Maynard, G., Kannan, R., Liu, J., Wang, W., Lam, T. K. T., Wang, X., Adamson, C., Hackett, C., Schwab, J. M., Liu, C., Leslie, D. P., Chen, D., Marino, R., Zafonte, R., Flanders, A., Block, G., Smith, E., Strittmatter, S. M., Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial. Lancet Neurol 22, 672–84 (2023).10.1016/S1474-4422(23)00215-6CrossRefGoogle Scholar
Hsiao, M.-C., Yu, P.-N., Song, D., Liu, C. Y., Heck, C. N., Millett, D., Berger, T. W., An in vitro seizure model from human hippocampal slices using multi-electrode arrays. J Neurosci Methods 244, 154–63 (2015).10.1016/j.jneumeth.2014.09.010CrossRefGoogle Scholar
Ammothumkandy, A., Ravina, K., Wolseley, V., Tartt, A. N., Yu, P.-N., Corona, L., Zhang, N., Nune, G., Kalayjian, L., Mann, J. J., Rosoklija, G. B., Arango, V., Dwork, A. J., Lee, B., a. D. Smith, J., Song, D., Berger, T. W., Heck, C., Chow, R. H., Boldrini, M., Liu, C. Y., Russin, J. J., Bonaguidi, M. A., Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy. Nat Neurosci 25, 493503 (2022).10.1038/s41593-022-01044-2CrossRefGoogle ScholarPubMed
Hurley, D., Immature astroglia in the hippocampus linked to mesial temporal lobe epilepsy. Neurology Today 22, 12 (2022).10.1097/01.NT.0000833140.99511.f6CrossRefGoogle Scholar
Ammothumkandy, A., Corona, L., Ravina, K., Wolseley, V., Nelson, J., Atai, N., Abedi, A., Jimenez, N., Armacost, M., D’Orazio, L. M., Zuverza-Chavarria, V., Cayce, A., McCleary, C., Nune, G., Kalayjian, L., Lee, D., Lee, B., Heck, C., Chow, R. H., Russin, J. J., Liu, C. Y., Smith, J. A. D., Bonaguidi, M. A., Human adult neurogenesis loss underlies cognitive decline during epilepsy progression. bioRxiv [Preprint] (2023). https://doi.org/10.1101/2022.09.12.507339.CrossRefGoogle Scholar
Bershteyn, M., Bröer, S., Parekh, M., Maury, Y., Havlicek, S., Kriks, S., Fuentealba, L., Lee, S., Zhou, R., Subramanyam, G., Sezan, M., Sevilla, E. S., Blankenberger, W., Spatazza, J., Zhou, L., Nethercott, H., Traver, D., Hampel, P., Kim, H., Watson, M., Salter, N., Nesterova, A., Au, W., Kriegstein, A., Alvarez-Buylla, A., Rubenstein, J., Banik, G., Bulfone, A., Priest, C., Nicholas, C. R., Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy. Cell Stem Cell 30, 1331–50.e11 (2023).10.1016/j.stem.2023.08.013CrossRefGoogle ScholarPubMed
Newswire, Globe, Neurona Therapeutics Presents Positive Clinical Update from NRTX-1001 Cell Therapy Trial in Adults with Drug-resistant Focal Epilepsy at American Academy of Neurology (AAN) 2024 Annual Meeting, BioSpace (2024). https://www.biospace.com/article/neurona-therapeutics-presents-positive-clinical-update-from-nrtx-1001-cell-therapy-trial-in-adults-with-drug-resistant-focal-epilepsy-at-american-academy-of-neurology-aan-2024-annual-meeting/.Google Scholar
Fairhall, A., Liu, C., Short Course: Neural Prosthetics and Brain Machine Interfaces (2019). https://www.sfn.org/-/media/SfN/Documents/NEW-SfN/Careers/2019-Short-Courses/20190911_2019_SC1_Agenda_Final.pdf.Google Scholar
Hochberg, L. R., Serruya, M. D., Friehs, G. M., Mukand, J. A., Saleh, M., Caplan, A. H., Branner, A., Chen, D., Penn, R. D., Donoghue, J. P., Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164–71 (2006).10.1038/nature04970CrossRefGoogle ScholarPubMed
Katyal, K. D., Johannes, M. S., Kellis, S., Aflalo, T., Klaes, C., McGee, T. G., Para, M. P., Shi, Y., Lee, B., Pejsa, K., Liu, C., Wester, B. A., Tenore, F., Beaty, J. D., Ravitz, A. D., Andersen, R. A., McLoughlin, M. P., A collaborative BCI approach to autonomous control of a prosthetic limb system, in 2014 IEEE International Conference on Systems, Man, and Cybernetics (SMC) (2014), https://ieeexplore.ieee.org/document/6974124), pp. 1479–82.Google Scholar
Collinger, J. L., Wodlinger, B., Downey, J. E., Wang, W., Tyler-Kabara, E. C., Weber, D. J., McMorland, A. J. C., Velliste, M., Boninger, M. L., Schwartz, A. B., High-performance neuroprosthetic control by an individual with tetraplegia. Lancet 381, 557–64 (2013).10.1016/S0140-6736(12)61816-9CrossRefGoogle Scholar
Klaes, C., Kellis, S., Aflalo, T., Lee, B., Pejsa, K., Shanfield, K., Hayes-Jackson, S., Aisen, M., Heck, C., Liu, C., Andersen, R. A., Hand shape representations in the human posterior parietal cortex. J. Neurosci. 35, 15466–76 (2015).10.1523/JNEUROSCI.2747-15.2015CrossRefGoogle ScholarPubMed
Bouton, C. E., Shaikhouni, A., Annetta, N. V., Bockbrader, M. A., Friedenberg, D. A., Nielson, D. M., Sharma, G., Sederberg, P. B., Glenn, B. C., Mysiw, W. J., Morgan, A. G., Deogaonkar, M., Rezai, A. R., Restoring cortical control of functional movement in a human with quadriplegia. Nature 533, 247–50 (2016).10.1038/nature17435CrossRefGoogle Scholar
Ajiboye, A. B., Willett, F. R., Young, D. R., Memberg, W. D., Murphy, B. A., Miller, J. P., Walter, B. L., Sweet, J. A., Hoyen, H. A., Keith, M. W., Peckham, P. H., Simeral, J. D., Donoghue, J. P., Hochberg, L. R., Kirsch, R. F., Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration. The Lancet 389, 1821–30 (2017).10.1016/S0140-6736(17)30601-3CrossRefGoogle Scholar
Musk, E., Neuralink, , An integrated brain-machine interface platform with thousands of channels. J Med Internet Res 21, e16194 (2019).10.2196/16194CrossRefGoogle ScholarPubMed
Flesher, S. N., Collinger, J. L., Foldes, S. T., Weiss, J. M., Downey, J. E., Tyler-Kabara, E. C., Bensmaia, S. J., Schwartz, A. B., Boninger, M. L., Gaunt, R. A., Intracortical microstimulation of human somatosensory cortex. Sci Transl Med 8, 361ra141 (2016).10.1126/scitranslmed.aaf8083CrossRefGoogle ScholarPubMed
Armenta Salas, M., Bashford, L., Kellis, S., Jafari, M., Jo, H., Kramer, D., Shanfield, K., Pejsa, K., Lee, B., Liu, C. Y., Andersen, R. A., Proprioceptive and cutaneous sensations in humans elicited by intracortical microstimulation. Elife 7, e32904 (2018).10.7554/eLife.32904CrossRefGoogle ScholarPubMed
Bashford, L., Rosenthal, I., Kellis, S., Pejsa, K., Kramer, D., Lee, B., Liu, C., Andersen, R. A., The neurophysiological representation of imagined somatosensory percepts in human cortex. J Neurosci 41, 2177–85 (2021).10.1523/JNEUROSCI.2460-20.2021CrossRefGoogle ScholarPubMed
Lee, B., Kramer, D., Armenta Salas, M., Kellis, S., Brown, D., Dobreva, T., Klaes, C., Heck, C., Liu, C., Andersen, R. A., Engineering artificial somatosensation through cortical stimulation in humans. Front Syst Neurosci 12, 24 (2018).10.3389/fnsys.2018.00024CrossRefGoogle ScholarPubMed
McCrimmon, C. M., Wang, P. T., Heydari, P., Nguyen, A., Shaw, S. J., Gong, H., Chui, L. A., Liu, C. Y., Nenadic, Z., Do, A. H., Electrocorticographic encoding of human gait in the leg primary motor cortex. Cereb Cortex 28, 2752–62 (2018).10.1093/cercor/bhx155CrossRefGoogle ScholarPubMed
Pu, H., Lim, J., Kellis, S., Liu, C. Y., Andersen, R. A., Do, A. H., Heydari, P., Nenadic, Z., Optimal artifact suppression in simultaneous electrocorticography stimulation and recording for bi-directional brain-computer interface applications. J Neural Eng 17, 026038 (2020).10.1088/1741-2552/ab82acCrossRefGoogle ScholarPubMed
Harkema, S., Gerasimenko, Y., Hodes, J., Burdick, J., Angeli, C., Chen, Y., Ferreira, C., Willhite, A., Rejc, E., Grossman, R. G., Edgerton, V. R., Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet 377, 1938–47 (2011).10.1016/S0140-6736(11)60547-3CrossRefGoogle ScholarPubMed
Wagner, F. B., Mignardot, J.-B., Le Goff-Mignardot, C. G., Demesmaeker, R., Komi, S., Capogrosso, M., Rowald, A., Seáñez, I., Caban, M., Pirondini, E., Vat, M., McCracken, L. A., Heimgartner, R., Fodor, I., Watrin, A., Seguin, P., Paoles, E., Van Den Keybus, K., Eberle, G., Schurch, B., Pralong, E., Becce, F., Prior, J., Buse, N., Buschman, R., Neufeld, E., Kuster, N., Carda, S., von Zitzewitz, J., Delattre, V., Denison, T., Lambert, H., Minassian, K., Bloch, J., Courtine, G., Targeted neurotechnology restores walking in humans with spinal cord injury. Nature 563, 6571 (2018).10.1038/s41586-018-0649-2CrossRefGoogle ScholarPubMed
Lorach, H., Galvez, A., Spagnolo, V., Martel, F., Karakas, S., Intering, N., Vat, M., Faivre, O., Harte, C., Komi, S., Ravier, J., Collin, T., Coquoz, L., Sakr, I., Baaklini, E., Hernandez-Charpak, S. D., Dumont, G., Buschman, R., Buse, N., Denison, T., van Nes, I., Asboth, L., Watrin, A., Struber, L., Sauter-Starace, F., Langar, L., Auboiroux, V., Carda, S., Chabardes, S., Aksenova, T., Demesmaeker, R., Charvet, G., Bloch, J., Courtine, G., Walking naturally after spinal cord injury using a brain-spine interface. Nature 618, 126–33 (2023).10.1038/s41586-023-06094-5CrossRefGoogle ScholarPubMed
Anumanchipalli, G. K., Chartier, J., Chang, E. F., Speech synthesis from neural decoding of spoken sentences. Nature 568, 493–8 (2019).10.1038/s41586-019-1119-1CrossRefGoogle ScholarPubMed
Moses, D. A., Metzger, S. L., Liu, J. R., Anumanchipalli, G. K., Makin, J. G., Sun, P. F., Chartier, J., Dougherty, M. E., Liu, P. M., Abrams, G. M., Tu-Chan, A., Ganguly, K., Chang, E. F., Neuroprosthesis for decoding speech in a paralyzed person with anarthria. N Engl J Med 385, 217–27 (2021).10.1056/NEJMoa2027540CrossRefGoogle Scholar
Willett, F. R., Avansino, D. T., Hochberg, L. R., Henderson, J. M., Shenoy, K. V., High-performance brain-to-text communication via handwriting. Nature 593, 249–54 (2021).10.1038/s41586-021-03506-2CrossRefGoogle ScholarPubMed
Willett, F. R., Kunz, E. M., Fan, C., Avansino, D. T., Wilson, G. H., Choi, E. Y., Kamdar, F., Glasser, M. F., Hochberg, L. R., Druckmann, S., Shenoy, K. V., Henderson, J. M., A high-performance speech neuroprosthesis. Nature 620, 1031–6 (2023).10.1038/s41586-023-06377-xCrossRefGoogle ScholarPubMed
Wandelt, S. K., Kellis, S., Bjånes, D. A., Pejsa, K., Lee, B., Liu, C., Andersen, R. A., Decoding grasp and speech signals from the cortical grasp circuit in a tetraplegic human. Neuron 110, 1777–87.e3 (2022).10.1016/j.neuron.2022.03.009CrossRefGoogle Scholar
Wandelt, S. K., Bjånes, D. A., Pejsa, K., Lee, B., Liu, C., Andersen, R. A., Representation of internal speech by single neurons in human supramarginal gyrus. Nat Hum Behav, doi: 10.1038/s41562-024-01867-y (2024).CrossRefGoogle Scholar
Naddaf, M., Brain-reading device is best yet at decoding “internal speech.” Nature, doi: 10.1038/d41586-024-01424-7 (2024).CrossRefGoogle Scholar
Hampson, R. E., Song, D., Robinson, B. S., Fetterhoff, D., Dakos, A. S., Roeder, B. M., She, X., Wicks, R. T., Witcher, M. R., Couture, D. E., Laxton, A. W., Munger-Clary, H., Popli, G., Sollman, M. J., Whitlow, C. T., Marmarelis, V. Z., Berger, T. W., Deadwyler, S. A., Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall. J Neural Eng 15, 036014 (2018).10.1088/1741-2552/aaaed7CrossRefGoogle ScholarPubMed
Roeder, B. M., Riley, M. R., She, X., Dakos, A. S., Robinson, B. S., Moore, B. J., Couture, D. E., Laxton, A. W., Popli, G., Munger Clary, H. M., Sam, M., Heck, C., Nune, G., Lee, B., Liu, C., Shaw, S., Gong, H., Marmarelis, V. Z., Berger, T. W., Deadwyler, S. A., Song, D., Hampson, R. E., Patterned hippocampal stimulation facilitates memory in patients with a history of head impact and/or brain injury. Front Hum Neurosci 16, 933401 (2022).10.3389/fnhum.2022.933401CrossRefGoogle ScholarPubMed
Ezzyat, Y., Wanda, P. A., Levy, D. F., Kadel, A., Aka, A., Pedisich, I., Sperling, M. R., Sharan, A. D., Lega, B. C., Burks, A., Gross, R. E., Inman, C. S., Jobst, B. C., Gorenstein, M. A., Davis, K. A., Worrell, G. A., Kucewicz, M. T., Stein, J. M., Gorniak, R., Das, S. R., Rizzuto, D. S., Kahana, M. J., Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun 9, 365 (2018).10.1038/s41467-017-02753-0CrossRefGoogle ScholarPubMed
Kragel, J. E., Ezzyat, Y., Lega, B. C., Sperling, M. R., Worrell, G. A., Gross, R. E., Jobst, B. C., Sheth, S. A., Zaghloul, K. A., Stein, J. M., Kahana, M. J., Distinct cortical systems reinstate the content and context of episodic memories. Nat Commun 12, 4444 (2021).10.1038/s41467-021-24393-1CrossRefGoogle ScholarPubMed
Sani, O. G., Yang, Y., Lee, M. B., Dawes, H. E., Chang, E. F., Shanechi, M. M., Mood variations decoded from multi-site intracranial human brain activity. Nat Biotechnol 36, 954–61 (2018).10.1038/nbt.4200CrossRefGoogle ScholarPubMed
Shanechi, M. M., Brain–machine interfaces from motor to mood. Nat Neurosci 22, 1554–64 (2019).10.1038/s41593-019-0488-yCrossRefGoogle ScholarPubMed
Thielen, B., Xu, H., Fujii, T., Rangwala, S. D., Jiang, W., Lin, M., Kammen, A., Liu, C., Selvan, P., Song, D., Mack, W. J., Meng, E., Making a case for endovascular approaches for neural recording and stimulation. J Neural Eng 20, 011001 (2023).10.1088/1741-2552/acb086CrossRefGoogle ScholarPubMed
Opie, N. L., John, S. E., Rind, G. S., Ronayne, S. M., Wong, Y. T., Gerboni, G., Yoo, P. E., Lovell, T. J. H., Scordas, T. C. M., Wilson, S. L., Dornom, A., T. Vale, T. O’Brien, J., Grayden, D. B., May, C. N., Oxley, T. J., Focal stimulation of the sheep motor cortex with a chronically implanted minimally invasive electrode array mounted on an endovascular stent. Nat Biomed Eng 2, 907–14 (2018).10.1038/s41551-018-0321-zCrossRefGoogle Scholar
Oxley, T. J., Opie, N. L., John, S. E., Rind, G. S., Ronayne, S. M., Wheeler, T. L., Judy, J. W., McDonald, A. J., Dornom, A., Lovell, T. J. H., Steward, C., Garrett, D. J., Moffat, B. A., Lui, E. H., Yassi, N., Campbell, B. C. V., Wong, Y. T., Fox, K. E., Nurse, E. S., Bennett, I. E., Bauquier, S. H., Liyanage, K. A., van der Nagel, N. R., Perucca, P., Ahnood, A., Gill, K. P., Yan, B., Churilov, L., French, C. R., Desmond, P. M., Horne, M. K., Kiers, L., S. Prawer, S. Davis, M., Burkitt, A. N., Mitchell, P. J., Grayden, D. B., May, C. N., O’Brien, T. J., Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity. Nat Biotechnol 34, 320–7 (2016).10.1038/nbt.3428CrossRefGoogle ScholarPubMed
Mitchell, P., Lee, S. C. M., Yoo, P. E., Morokoff, A., Sharma, R. P., Williams, D. L., MacIsaac, C., Howard, M. E., Irving, L., Vrljic, I., Williams, C., Bush, S., Balabanski, A. H., Drummond, K. J., Desmond, P., Weber, D., Denison, T., Mathers, S., O’Brien, T. J., Mocco, J., Grayden, D. B., Liebeskind, D. S., Opie, N. L., Oxley, T. J., Campbell, B. C. V., Assessment of safety of a fully implanted endovascular brain-computer interface for severe paralysis in 4 patients: the Stentrode With Thought-Controlled Digital Switch (SWITCH) study. JAMA Neurol 80, 270–8 (2023).10.1001/jamaneurol.2022.4847CrossRefGoogle Scholar
Macé, E., Montaldo, G., Cohen, I., Baulac, M., Fink, M., Tanter, M., Functional ultrasound imaging of the brain. Nat Methods 8, 662–4 (2011).10.1038/nmeth.1641CrossRefGoogle ScholarPubMed
Norman, S. L., Maresca, D., Christopoulos, V. N., Griggs, W. S., Demene, C., Tanter, M., Shapiro, M. G., Andersen, R. A., Single trial decoding of movement intentions using functional ultrasound neuroimaging. Neuron 109, 1554–66.e4 (2021).10.1016/j.neuron.2021.03.003CrossRefGoogle ScholarPubMed
Griggs, W. S., Norman, S. L., Deffieux, T., Segura, F., Osmanski, B.-F., Chau, G., Christopoulos, V., Liu, C., Tanter, M., Shapiro, M. G., Andersen, R. A., Decoding motor plans using a closed-loop ultrasonic brain–machine interface. Nat Neurosci 27, 196207 (2023).10.1038/s41593-023-01500-7CrossRefGoogle ScholarPubMed
Rabut, C., Norman, S. L., Griggs, W. S., Russin, J. J., Jann, K., Christopoulos, V., Liu, C., Andersen, R. A., Shapiro, M. G., A window to the brain: ultrasound imaging of human neural activity through a permanent acoustic window. bioRxiv [Preprint] (2023). https://doi.org/10.1101/2023.06.14.544094.CrossRefGoogle Scholar
Morrell, M. J., RNS System in Epilepsy Study Group, Responsive cortical stimulation for the treatment of medically intractable partial epilepsy. Neurology 77, 1295–304 (2011).10.1212/WNL.0b013e3182302056CrossRefGoogle Scholar
Lee, B., Zubair, M. N., Marquez, Y. D., Lee, D. M., Kalayjian, L. A., Heck, C. N., Liu, C. Y., A single-center experience with the NeuroPace RNS system: A review of techniques and potential problems. World Neurosurg 84, 719–26 (2015).10.1016/j.wneu.2015.04.050CrossRefGoogle ScholarPubMed
Levy, R. M., Harvey, R. L., Kissela, B. M., Winstein, C. J., Lutsep, H. L., Parrish, T. B., Cramer, S. C., Venkatesan, L., Epidural electrical stimulation for stroke rehabilitation: Results of the prospective, multicenter, randomized, single-blinded Everest trial. Neurorehabil Neural Repair 30, 107–19 (2016).10.1177/1545968315575613CrossRefGoogle ScholarPubMed
Harvey, R. L., Edwards, D., Dunning, K., Fregni, F., Stein, J., Laine, J., Rogers, L. M., Vox, F., Durand-Sanchez, A., Bockbrader, M., Goldstein, L. B., Francisco, G. E., Kinney, C. L., Liu, C. Y., NICHE Trial Investigators, Randomized sham-controlled trial of navigated repetitive transcranial magnetic stimulation for motor recovery in stroke. Stroke 49, 2138–46 (2018).10.1161/STROKEAHA.117.020607CrossRefGoogle Scholar
Edwards, D. J., Liu, C. Y., Dunning, K., Fregni, F., Laine, J., Leiby, B. E., Rogers, L. M., Harvey, R. L., Electric field navigated 1-Hz rTMS for poststroke motor recovery: The E-FIT randomized controlled trial. Stroke 54, 2254–64 (2023).10.1161/STROKEAHA.123.043164CrossRefGoogle ScholarPubMed
Dawson, J., Liu, C. Y., Francisco, G. E., Cramer, S. C., Wolf, S. L., Dixit, A., Alexander, J., Ali, R., Brown, B. L., Feng, W., L. DeMark, L. Hochberg, R., Kautz, S. A., Majid, A., O’Dell, M. W., Pierce, D., Prudente, C. N., Redgrave, J., Turner, D. L., Engineer, N. D., Kimberley, T. J., Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet 397, 1545–53 (2021).10.1016/S0140-6736(21)00475-XCrossRefGoogle ScholarPubMed
Liu, C. Y., Russin, J., Adelson, D. P., Jenkins, A., Hilmi, O., Brown, B., Lega, B., Whitworth, T., Bhattacharyya, D., Schwartz, T. H., Krishna, V., Williams, Z., Uff, C., Willie, J., Hoffman, C., Vandergrift, W. A., Achrol, A. S., Ali, R., Konrad, P., Edmonds, J., Kim, D., Bhatt, P., Tarver, B. W., Pierce, D., Jain, R., Burress, C., Casavant, R., Prudente, C. N., N. D. Engineer, Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial. J Clin Neurosci 105, 122–8 (2022).10.1016/j.jocn.2022.09.013CrossRefGoogle ScholarPubMed
Dawson, J., Abdul-Rahim, A. H., Kimberley, T. J., Neurostimulation for treatment of post-stroke impairments. Nat Rev Neurol 20, 259–68 (2024).10.1038/s41582-024-00953-zCrossRefGoogle ScholarPubMed
Bowles, S., Hickman, J., Peng, X., Williamson, W. R., Huang, R., Washington, K., Donegan, D., Welle, C. G., Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement. Neuron 110, 2867–85.e7 (2022).10.1016/j.neuron.2022.06.017CrossRefGoogle ScholarPubMed
Grover, S., Wen, W., Viswanathan, V., Gill, C. T., Reinhart, R. M. G., Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Nat Neurosci 25, 1237–46 (2022).10.1038/s41593-022-01132-3CrossRefGoogle ScholarPubMed
Kreydin, E. I., Gad, P., Gao, B., Liu, C. Y., Ginsberg, D. A., Jann, K., The effect of stroke on micturition associated brain activity: A pilot fMRI study. Neurourology and Urodynamics 39, 2198–205 (2020).10.1002/nau.24473CrossRefGoogle ScholarPubMed
Kreydin, E. I., Abedi, A., Montero, V. S., Morales, L., Jen, R., Perez, L., La Riva, A., Kohli, P., Liu, C. Y., Ginsberg, D. A., Gad, P., Edgerton, V. R., Jann, K., A pilot study of the effect of transcutaneous spinal cord stimulation on micturition-related brain activity and lower urinary tract symptoms after stroke. J Urol 211, 294304 (2024).10.1097/JU.0000000000003776CrossRefGoogle ScholarPubMed
Hastings, S., Zhong, H., Feinstein, R., Zelczer, G., Mitrovich, C., Gad, P., Edgerton, V. R., A pilot study combining noninvasive spinal neuromodulation and activity-based neurorehabilitation therapy in children with cerebral palsy. Nat Commun 13, 5660 (2022).10.1038/s41467-022-33208-wCrossRefGoogle ScholarPubMed
Na, S., Russin, J. J., Lin, L., Yuan, X., Hu, P., Jann, K. B., Yan, L., Maslov, K., Shi, J., Wang, D. J., Liu, C. Y., Wang, L. V., Massively parallel functional photoacoustic computed tomography of the human brain. Nat Biomed Eng 6, 584–92 (2022).Google ScholarPubMed
Agyeman, K. A., Lee, D. J., Russin, J., Kreydin, E. I., Choi, W., Abedi, A., Lo, Y. T., Cavaleri, J., Wu, K., Edgerton, V. R., Liu, C., Christopoulos, V. N., Functional ultrasound imaging of the human spinal cord. Neuron 112, 1710–22.e3 (2024).10.1016/j.neuron.2024.02.012CrossRefGoogle ScholarPubMed
Agyeman, K. A., Lee, D. J., Abedi, A., Sakellaridi, S., Kreydin, E. I., Russin, J., Lo, Y. T., Wu, K., Choi, W., Edgerton, V. R., Liu, C., Christopoulos, V. N., Human spinal cord activation during filling and emptying of the bladder. bioRxiv [Preprint] (2024). https://doi.org/10.1101/2024.02.16.580736.CrossRefGoogle Scholar
Huang, Y. X., Mahler, S., Dickson, M., Abedi, A., Tyszka, J. M., Lo, Y. T., Russin, J., Liu, C., Yang, C., A compact and cost-effective laser-powered speckle visibility spectroscopy (SVS) device for measuring cerebral blood flow. ArXiv, arXiv:2401.16592v2 (2024).10.1117/1.JBO.29.6.067001CrossRefGoogle Scholar

Accessibility standard: Inaccessible, or known limited accessibility

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

The PDF of this book is known to have missing or limited accessibility features. We may be reviewing its accessibility for future improvement, but final compliance is not yet assured and may be subject to legal exceptions. If you have any questions, please contact accessibility@cambridge.org.

Content Navigation

Table of contents navigation
Allows you to navigate directly to chapters, sections, or non‐text items through a linked table of contents, reducing the need for extensive scrolling.
Index navigation
Provides an interactive index, letting you go straight to where a term or subject appears in the text without manual searching.

Reading Order & Textual Equivalents

Single logical reading order
You will encounter all content (including footnotes, captions, etc.) in a clear, sequential flow, making it easier to follow with assistive tools like screen readers.
Short alternative textual descriptions
You get concise descriptions (for images, charts, or media clips), ensuring you do not miss crucial information when visual or audio elements are not accessible.

Visual Accessibility

Use of colour is not sole means of conveying information
You will still understand key ideas or prompts without relying solely on colour, which is especially helpful if you have colour vision deficiencies.

Structural and Technical Features

ARIA roles provided
You gain clarity from ARIA (Accessible Rich Internet Applications) roles and attributes, as they help assistive technologies interpret how each part of the content functions.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×